The long-term goal of this research project is to gain a better understanding of the pathogenic mechanisms underlying the death of experimental animals poisoned with bacterial endotoxin or infected with gram negative bacteria. More specifically, this project is designed to clarify the mechanisms of selected metabolic alterations in the host following endotoxin poisoning and to determine their significance. Projects currently under study include (a) a comparison of the rate of conversion of DL-tryptophan (benzene Ring-C14) to C14O2 in normal and endotoxin-poisoned rats with a similar ability in perfused rat livers isolated from either normal or endotoxin-poisoned rats or livers exposed to various doses of endotoxin in vitro, (b) a light and electron microscopic characterization of freshly isolated and perfused liver from normal and endotoxin-poisoned animals, and (c) the role of carbohydrate metabolism in the hyperreactivity of endotoxin-poisoned adrenalectomized mice to tryptophan.